Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI
Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI
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DOI：
10.3109/09553002.2016.1168533
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发表时间：
2016-11-01
影响因子：
2.6
通讯作者：
Kotzerke, Joerg
中科院分区：
文献类型：
--
作者：
Maucksch, Ute;Runge, Roswitha;Kotzerke, Joerg
目的：除了伽马辐射外，99m还能发射路径从纳米到微米的低能量俄歇电子，不能用于诊断程序；然而，它们经常被讨论用于治疗应用。材料和方法：用大鼠甲状腺FRTL-5细胞定量测定了[~(99)m]-高铁酸盐(~(99)T)、[~(99)m]-高铁酸盐(~(99)m)、[~(99)m]~(99)Tc-六甲基丙氨肟(~(99)m-HMPO)和~([Tc-99m]Tc-hexakis-2-methoxyisobutylisonitrile)在细胞内的摄取和亚细胞分布。用晚期磷酸化组蛋白H_2AX(H_2AX)灶作为未修复DNA双链断裂(DNA-DSB)和克隆形成细胞存活的标志物进行放射毒性比较。结果：TC-99m-HMPAO对细胞核和细胞膜/细胞器的摄取明显高于TC-99m-高铁酸盐和TC-99m-MIBI。集落形成实验表明，99m-高铁酸盐和99m-HMPAO对细胞存活率的影响相似。在估算的核剂量方面，TC-99m-MIBI具有较低的放射毒性，与其他TC-99m示踪剂相比，Tc-99m-MIBI诱导的H_2AX灶数目最少，而T_c-99m-HMPAO诱导的H_2AX灶数目少于T_c-99m-高铁氧体。结论：克隆形成细胞的存活不完全由DNA-DSB反应决定。这一发现可能表明核外放射敏感靶点参与了细胞失活。例如，TC-99m-HMPAO可影响线粒体或细胞膜。
Purpose: In addition to gamma radiation, Tc-99m emits low-energy Auger electrons with path-lengths of nanometers to micrometers that cannot be utilized for diagnostic procedures; however, they have frequently been discussed for therapeutic applications. We compared radiotoxicity of three Tc-99m-labeled radiopharmaceuticals with differences in the subcellular distribution.Materials and methods: The intracellular radionuclide uptake and subcellular distribution of [Tc-99m]-pertechnetate (Tc-99m-pertechnetate), [Tc-99m]Tc-hexamethyl-propylene-aminoxime (Tc-99m-HMPAO) and [Tc-99m]Tc-hexakis-2-methoxyisobutylisonitrile (Tc-99m-MIBI) were quantified in rat thyroid FRTL-5 cells. Radiotoxicity was compared using late phosphorylated histone H2AX (H2AX) foci as a marker for unrepaired DNA double-strand breaks (DNA-DSB) and clonogenic cell survival.Results: Tc-99m-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than Tc-99m-pertechnetate or Tc-99m-MIBI. The colony-forming assay showed that Tc-99m-pertechnetate and Tc-99m-HMPAO caused a similar reduction in cell survival. Tc-99m-MIBI is less radiotoxic in terms of the estimated nucleus dose and induced the fewest number of H2AX foci compared with the other Tc-99m-tracers, and Tc-99m-HMPAO induced a fewer number of H2AX foci than Tc-99m-pertechnetate.Conclusions: Our findings reveal that clonogenic cellular survival is not solely determined by the DNA-DSB response. This finding may suggest the involvement of extra-nuclear radiosensitive targets in cell inactivation. For example, the mitochondria or the cell membrane could be affected by Tc-99m-HMPAO.